Abstract 5539: Nivolumab after cyclophosphamide and doxorubicin induction therapy in previously treated advanced non-squamousl non-small cell lung cancer with PD-L1&amp;lt;10%
Authors: Beung-Chul Ahn, Hyae Young Kim, Geon Kook Lee, Sang-Jin Lee, Ji-Eun Hwang, Kyoungsuk Kwon, Youngjoo Lee, Ji-Youn Han
Journal: Cancer Research (2022)

Abstract Purpose: Immune checkpoint inhibitor(ICI) therapies are a standard treatment for advanced non-small-cell lung cancer(NSCLC). However, the beneficial effects are limited to a small subset of patients. Primary resistance to ICIs has been attributed to various kinds of suppressive immune regulatory cells in tumor-microenvironment. Different strategies have thus been explored to escape from immune evasion by depleting and/or inactivating these regulatory cells. Given the immune-modulating effects of low doses of cyclophosphamide and adriamycin (CA), we assessed the efficacy of CA induction therapy to modulate the antitumor effect of the nivolumab in advanced NSCLC. Methods: This was a single center, open-label, single arm, phase II trial of nivolumab after CA induction therapy in previously treated advanced non-squamous NSCLC with PD-L1&amp;lt;10%. Patients received cyclophosphamide(500mg/m2) and doxorubicin(50mg/m2) every 3weeks with additional nivolumab 360mg from the start of second cycle. After 4 cycles of induction therapy nivolumab 480mg was administered every 4weeks until disease progression or unacceptable toxicity. Assessments were performed every 4 weeks. The primary end point was objective response rate (ORR); secondary end points were progression-free survival (PFS), overall survival(OS) and safety. Level of various immune cells including myeloid-derived suppressor cells (MDSC), cytotoxic CD8+T-cell and regulatory T cells were measured by flow cytometry. Results: A total of 22 patients were enrolled; the median age, 61 years old; female, 81%; adenocarcinoma histology, 76.2%; and current or former smoker, 26.9%. The ORR and disease control rate (DCR) were 9.1% (95% confidence interval [CI], 1.9 -26.1)) and 22.7% (95% CI, 9.2-42.9) respectively. The median PFS and OS were 2.4 months (95% CI, 1.3-3.5) and 11.6 months (95% CI, 5.3-18.0) respectively. Though there were no significant safety signals during the trial, 72% of patients had grade 3 or 4 hematologic toxicities including neutropenia and anemia during CA combination. Regarding MDSC (HLA-DR-Lin-CD11b+CD33+) level, two patients with good response correlatively maintained the low ratio (&amp;lt;1) of MDSC to CD8+T-cell throughout the treatment. Conclusions: Our study didn’t meet the primary endpoint. However, CA induction prior to nivolumab showed an immune-modulating potential by decreasing MDSC in two responders. Further augmentation studies for enhancing ICIs response are warranted. As more patients gets ICIs, combination strategy with various immune modulator harbors great potential to eliminate the immunosuppressive mechanism within the tumor microenvironment architecture. Citation Format: Beung-Chul Ahn, Hyae Young Kim, Geon Kook Lee, Sang-Jin Lee, Ji-Eun Hwang, Kyoungsuk Kwon, Youngjoo Lee, Ji-Youn Han. Nivolumab after cyclophosphamide and doxorubicin induction therapy in previously treated advanced non-squamousl non-small cell lung cancer with PD-L1&amp;lt;10% [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5539.